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Nature 439, 480-483 (26 January 2006) | doi:10.1038/nature04436; Received 9 September 2005; Accepted 25 October 2005

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Pregnenolone stabilizes microtubules and promotes zebrafish embryonic cell movement

Hwei-Jan Hsu1,2, Ming-Ren Liang3, Chao-Tsen Chen3 & Bon-chu Chung1

  1. Institute of Molecular Biology, Academia Sinica, Nankang, Taipei 11529, Taiwan
  2. Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11490, Taiwan
  3. Department of Chemistry, National Taiwan University, Taipei 10617, Taiwan

Correspondence to: Bon-chu Chung1 Correspondence and requests for materials should be addressed to B.-c.C. (Email: mbchung@sinica.edu.tw).

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Embryonic cell movement is essential for morphogenesis and the establishment of body shapes1, 2, but little is known about its mechanism. Here we report that pregnenolone, which is produced from cholesterol by the steroidogenic enzyme Cyp11a1 (cholesterol side-chain cleavage enzyme, P450scc)3, functions in promoting cell migration during epiboly. Epiboly is a process in which embryonic cells spread from the animal pole to cover the underlying yolk. During epiboly, cyp11a1 is expressed in an extra-embryonic yolk syncytial layer4. Reducing cyp11a1 expression in zebrafish using antisense morpholino oligonucleotides did not perturb cell fates, but caused epibolic delay. This epibolic defect was partially rescued by the injection of cyp11a1 RNA or the supplementation of pregnenolone. We show that the epibolic delay is accompanied by a decrease in the level of polymerized microtubules, and that pregnenolone can rescue this microtubule defect. Our results indicate that pregnenolone preserves microtubule abundance and promotes cell movement during epiboly.

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